Intermittent theta burst stimulation over the left prefrontal cortex: no additional effect for virtual reality exposure therapy in acrophobia—a randomized trial

Abstract Anxiety disorders are the most prevalent mental health conditions. Besides psycho-pharmacotherapy, cognitive behavioral therapy with an exposure-based approach is considered the gold standard. However, not all patients benefit from this approach. Here, we aimed to translate laboratory findings on enhanced fear extinction with repetitive transcranial magnetic stimulation (TMS) to the clinic. In this double-blind, randomized, placebo-controlled clinical trial, 76 participants with acrophobia received an activating intermittent theta burst stimulation (iTBS) targeting the left posterior prefrontal cortex immediately before two virtual reality exposure therapy sessions. Phobic symptoms were assessed at baseline, post-intervention, and a 6-month follow-up. Results revealed a significant reduction in phobic symptoms from baseline to post-assessment and follow-up and confirmed the efficacy of virtual reality exposure therapy as a treatment for specific phobias. Interestingly, no additional effect was observed for active iTBS compared to sham iTBS. Our post-hoc analyses argue for an individualized TMS application. Further research is needed to determine optimal TMS parameters and validate these results in clinical trials, accounting for methodological and inter- and intra-individual variability, as well as alternative therapeutic processes.